Method of preparing antipyrine



9 the reaction mixture to hold in solutionthe I UNI ED-STATES.

Patented July is, 19

tel 8.5031;

CHARLESJ'. smegma AND CLAIRENCECQ soHwEGL n; or MIDLAND, MIC-me n;

ASSIGNORS TO THE now CHEMICAL comrnny, orumrnnnnqanonrqnn, A com RATION OF MICHIGAN No Drawing. 1

The present invention relates" to the prep- Our invention deals with a procession the treatment of antipyrine-hydrobromide formed by methylating phenyl-methyl-pyrazolone with methyl bromide and methylah cohol wherein antipyrine; is prepared therefrom and our improvements ,include the use of suitable novel solvents and procedures.

To the accomplishment ofthe foregoing and related ends, the, invention,;'then, consists of the steps hereinafter fully described and-particularly" pointed out in the claims,

the following'description setting forth in detail several modes of carrying out the 'invention, such disclosed modes illustrating, how p described, that'is, in batches, or the oil and' ilqwater may be passed through av series of: r i

ever, but several of the various ways inwhich the principle of the invention may be used.

By 1 former procedure antipyrine-hydrobromide was poured in the'hot liquidstate into a caustic soda solution and benzene mixture. "The sodium bromide-in aqueous solution was separatedj'from the reaction mixture and the antipyrine was crystallized by cooling from the resultingbenzene solution 6 thereof. Antipyrine crystals so obtained are colored and impure and must be recrystal lized many times from water and finally from'alcohol to obtain a satisfactory prod By our procedure "we 1 run 1 the hot liquid.

about two volumes of chlorobenzene to one volume :of 40 per cent caustic soda solution.

Thisproporti'on' provides suflicient water in cooling, at first, and addingheattoward the end of the Ireaction. .Anexcess of caustic soda is used, about one weight of antipyr ne rated from the oil layer of the reaction mix- 'pyrine therein. The chlorobenzene; used may ,be fresh or recovered, ,as convenient; i ".lfhe-isoiy, k I obtained hotchlor'obenzene solution oianti-f pyrine is then filtered hot to separate. onjtheif i 1 filter the impuritiesflinsolubleinthesolvent:

The filtrate is thenco'oled tocrystaljlize'out v If mnrnon or ranrnnme ANTIPY NE- Application filed September 18, 1931. Serial No. 563,672;

ture. The oil layer'is achlorobenzenesolua eon. of-antipyrine. The so derived: oil layer is then preferably cooled and toitlis added cold water followed by mixing, settling and pyrine is washed out, orextracted asawa- .ter solutionfthereof,leaving the chlorobenzene oil layer containingunextractedyanti pyrineutogether with 'chlorobenzene-soluble impurities. The waterjwashing, or 'extrac-\... r tion,'step is repeated a number of timesuntil F all or substantially allof the antipyrine has '1 l been extracted from the oil layer." i-In=prac tice four washesare employed, and a reduced I volume of water is used for each succeeding (59 I mixing. and separating steps in countercurrent to accomplishthe extraction 1n a contlnuous or semr-contln'uous manner; 'The e'ximmaterial to the principle offour invention.

The wash 'waterswcontaining theantipyrine are run into menuand evaporated,

preferably under reduced pressure suchias a 1 vacuumof 25 inches of mercury. The. Wash 5:39 waters may be introduced intoglthe stilllas obtained and evaporated while further washings' are being conducted. JAllfthe wateris evaporated" in the still to leave ia residue of I j hot, liquid antipyrine which co ever, watersoluble impurities. H Chlorobenzeneisrun into the still and heat I applied to dissolve the stillQr'esidue of an ti'-- '1' j antipyrine which isseparatediromthe mothe er liquor by draining, wheellng, -ietc.', y and,

'jconstitutes, after drying, a finished-product ofsuperiorquality is white and's b Y stantially pure.

, The mother liquors 7 separation, whereby'a portion ofthe. anti-i21 1 act procedure in the water extracting steps is r step may be worked up in any suitable man ner. They may, for instance, be concentrated by evaporation and cooled to obtain second crop of crystals, such crystals, if not of satisfactory purity, may be dissolved in ice water, filtered, and the solution evaporated to obtain an antipyrine residue which, after so; lution 1n .chlorobenzene, may be cooled and again crystallized therefrom. Mother liq-r uors may, however, be extracted with large volumes of water to recover antipyrine therefrom in a manner similar to that previously outlined forv the oil layerof the reaction mixture.

The chlorobenzene residues may be dis tilled or otherwise purified to recover chlorobenzene therefrom for reuse any part of the process, and in general the chlorobenzene may'b'e recycledin the process with suitable purification. y I

We find chlorobenzene tobe a convenient solvent and to possess properties highly advantageous in the'productionof antipyrine.

I ,Its high boiling point substantially avoids loss by evaporationin filtering. centrifuging,

handling, etc; contrasting in these properties with benzene and other more volatile solvents heretofore employed, use of which involves considerable evaporation losses. Its specific gravity facilitates separation from the water It may be obtained pure extraction layer. and readily recovered in a pure state for re use. It-has a high flash-point which reduces fire hazard. It dissolves its own weight of antipyrine and dissolves oily impurities, re-

' taining same in an effective manner during thewater extraction steps."

. Caustic potash, carbonate or bi-carbonate of sodium or potass'iu'm,lime, magnesia or other bases which will react maybe employed instead of caustic soda, but the latter is preferable when cheaplyc'onvenient.

Byproceeding in accordance with the steps I of ourinvention as hereinbefore set forth, the manufacture of antipyrine may be conducted with a reduced amount of equipment, in shorter time with lesslabor, and with con- I servation of materials.

The product, moreover, is of high purity, White, and meetsthe requirements of, the trade. H V Although'we prefer to use mono-chloro benzene as the. organic solvent, water extraction s advantageous whatever solvent "be of extracting thef antipyrine from the solvent solution thereof with water to leave the solvent-soluble impurities behind, persist with 0 such other solvents.

used, hence any suitable water immiscible solvent may be employediand the advantages Other modes of applying the principle of our invention may be employed instead of theiones explamed, change be ng made as regards'the method herein disclosed, provided the step-orsteps-stated by any of-the following claims or thoequivalent of such stated step or steps be employed.

lVo therefore particularly point out and distinctly claim as our invention it'l 1e method of preparing antipyrine I0 which comprises macting anti'pyrine-hydro'- broniioe with an aqueous solution of an alkali in the presence of solventimmiscible with water whileagitatingthe reaction mixture,

separating from the reaction mixture a solution of antipyrinein the solvent,extraoting theantipyrine from said solution with water, evaporating the-water therefrom to leave a residue of antipyrine, and recrystallizing the antipyrine from monochlorobenzene.

2. The method ofipreparing antipyrine y from antipyrine-hydrobmmide by I reaction with an alkali, which comprises 'mixing the hot liquid hydrobromide-with a mixture of about one volume of a 40 per cent caustic soda? 35 water solution and two volumes of chlorobenzene 1n the ratio of about one weight of the hydrobromide to one weight of the chlorobenzene while maintaining. the temperature :of the reaction mixture atabout 65 OQ settlingand extracting the antipyrine from the resulting; oil layerwith water. I

, 3. The method of preparing antipyrine from antipyrine hydrobro'inide by reaction with an alkali, Which-comprisesmixing the hot liquid hydrobromide with a mixture of about one volumeof a 40 per cent caustic soda water solution and two volumes oflchlorobenzene 1n the ratio of about one weight of the hydrobromide to one weight of the-chlo-" robenzene while' maintaining the temperature of the reaction m xture at about65 (l,

settling,and extracting the antipyrine from about one volume of a 40 per cent caustic soda water solution and two volumes of chlorobenzenein the ratio of about one weight of,

. l" the hvdrobromide to one, weight of the chloa robenzene while'maintaining the tem perae t ire of the reaction mixture at about 65 0., sottlin and extracting the antipyrine from the resuling oil layer with water, evaporatg ingg'water from the Water extract solution of antipyrine,preferably under reduced pressure, to obtain a residue of the latter, dissolving;saidresidue in chlorobenzene and coolingto obtain crystals of antipyrine. 12;; The method of separating antipyrine from a reaction 'solution thereof; in chlorobenzene, which comprises washing the ,solution with water to extract therefrom antipy .rine asawater solution thereof,'evaporating the water from such solution to leeve e residue of antipyrine, dissolving the residue in hot chlorobenzene, and coohng the solution,

to crystallize the antipyrine I 6. In a method ef preparing antipyrine from entipyrine-hydrobromicle by reaction with an alkali, the steps which consis't in so reacting in the presence of chlorobenzene a solvent for entipyrine, and extracting antilution. thereof with water.

7. In amethod of preparinggentipyrine v wherein a soluticn ef antiplyrine n e'solvent;

immiscible with water obtaine'dfthe' step which consists in extracting: he .vntip yrine fromsjuch solution with cold water. v I .4 I f.

" CHARLES 9LT. YSTROSACKER. 1f;- 7 r 1 L RE EQS HW G ER';

pyrine from the resultingchlorehenienefscf 1 

